Is FDPS p.Pro16Leu (c.47C>T) pathogenic?

FDPS p.Pro16Leu (c.47C>T) is classified Uncertain significance in FDPS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-09). AlphaMissense: likely benign (0.1681); Ultra-rare (popmax 0.0446%, sas).

How common is FDPS p.Pro16Leu (c.47C>T) in the general population?

FDPS p.Pro16Leu (c.47C>T) is ultra-rare (popmax 0.0446%, sas) (gnomAD).

What do computational predictors say about FDPS p.Pro16Leu (c.47C>T)?

AlphaMissense predicts likely benign (score 0.1681) — an in-silico prediction, not a clinical call.

FDPS p.Pro16Leu

c.47C>T · rs142276507 · VCV2326500

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1681 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0446%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1681	likely benign
REVEL	0.208	benign-leaning
SaProt	LLR -7.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 0.47, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 11 kb · p 1.1e-06 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0446% South Asian · 39/87,474 alleles

Filtering AF 0.0335% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0296%

Overall 0.0282% 445/1,578,498 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0446%	2,243
Middle Eastern	0.0364%	2,747
European (non-Finnish)	0.0331%	3,026
Remaining individualsnot grpmax-eligible	0.0279%	3,583
African / African-American	0.00403%	24,789
Admixed American	0.00179%	55,862

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: FDPS
Protein: p.Pro16Leu
Coding: c.47C>T
MANE Select: NM_002004
dbSNP: rs142276507
Type: single nucleotide variant
Location: chr1:155309836 (GRCh38)
Gene constraint: LOEUF 0.744 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.27 · 92 PDB

Full FDPS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FDPS c.684+2T>G Likely pathogenic ★ same type
FDPS p.Ala119Val Uncertain significance ★ ⚠ same type
FDPS p.Arg110Gly Uncertain significance ★ ⚠ same type
FDPS p.Arg110Trp Uncertain significance ★ ⚠ same type
FDPS p.Arg214Gln Uncertain significance ★ ⚠ same type
FDPS p.Arg23Gln Uncertain significance ★ ⚠ same type
FDPS p.Arg23Trp Uncertain significance ★ ⚠ same type
FDPS p.Arg25Lys Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/fdps-p-pro16leu (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown